Impact of incarceration experiences on reported HIV status and associated risk behaviours and disease comorbidities.

BACKGROUND: The Russian human immunodeficiency virus (HIV) epidemic among people who inject drugs (PWID) originated in Kaliningrad, but research into risk behaviours among PWID has been lacking. The potential for heterosexual spread has not been analysed. METHODS: A sample of PWID was accrued using two methods. A questionnaire was administered to assess HIV-related risk behaviours for parenteral and sexual transmission, sociodemographic factors, HIV knowledge and attitudes about sexual risks. Data were analysed focusing on the role of imprisonment, factors associated with awareness of being HIV infected and condom use. RESULTS: More than a quarter of the sample reported having been diagnosed with HIV infection, with higher prevalence among women and those with a history of incarceration. More than half reported having been diagnosed with hepatitis C virus infection. Those reporting being HIV positive were less likely to distribute used syringes to other PWID and more likely to have used a condom the last time they had sex. A history of incarceration was associated with higher rates of receptive syringe sharing among those not having ever received an HIV-positive diagnosis and a lower likelihood of believing that condoms are needed when having sex with a casual partner. CONCLUSION: Although extensive HIV testing has alerted many PWID to their HIV-positive status, which is associated with less distributive syringe sharing and higher likelihood of condom use, substantial risk for parenteral and especially sexual HIV transmission remains. More active prevention programs will be required to control the heterosexual spread of HIV.

The relation of the level of serum anti-TF, -Tn and -alpha-Gal IgG to survival in gastrointestinal cancer patients.

OBJECTIVE: To evaluate the relation of the level of serum anti-TF, -Tn and -αGal carbohydrate antibodies to survival in gastrointestinal cancer patients. METHODS: The level of anti-TF (Thomsen-Friedenreich antigen), -Tn and -αGal IgG was analysed in the serum of patients with gastric (n = 83) and colorectal (n = 51) cancers in the long-term follow-up, using ELISA with polyacrylamide glycoconjugates. To evaluate overall survival and the risk of death, the Kaplan-Meier method and the Cox proportional hazards model were used in the univariate analysis of patients groups. RESULTS: A significantly better survival was observed: (1) in patients with an increased level of anti-TF antibodies (all, stage III, T2-4, N1-2 and G3; P = 0.004-0.038, HR = 0.16-0.46); and (2) in patients with an increased level of anti-Tn antibodies (G1-2 tumors; P = 0.034-0.042, HR = 0.34-0.47). A significantly worse survival was observed in gastrointestinal, gastric and colorectal groups with an increased level of serum anti-αGal antibodies. This association depended on the patho-morphology of tumors (all, stages I-II, III, T2-4, N0, N1-2 and G1-2; P = 0.006-0.048, HR = 1.99-2.33). In the combined assessment of the anti-TF and -αGal antibodies level of the whole gastrointestinal group (n = 53), P = 0.002, HR = 0.25, 95% CI 0.094-0.655. In the follow-up, the survival time was shorter in patients whose level of anti-αGal antibodies rose (P = 0.009-0.040, HR = 2.18-4.27). The level of anti-TF antibodies inversely correlated with neutrophil/lymphocyte ratio (NLR, r = - 0.401, P = 0.004, n = 49). Patients with a higher level of anti-αGal antibodies and NLR values demonstrated a significantly worse survival (P = 0.009, HR = 2.98, n = 48). CONCLUSIONS: The preoperative levels of anti-TF, -Tn and -αGal antibodies and their dynamics are of prognostic significance. The method for the determination of circulating anti-carbohydrate antibodies may be a useful supplement in clinical outcome assessment.

Immunoglobulin G Fc N-glycan profiling in patients with gastric cancer by LC-ESI-MS: relation to tumor progression and survival.

The IgG Fc glycans strongly influence the Fcγ receptor interactions and Fc-mediated effector mechanisms. Changes in the structure of IgG glycans are associated with various diseases, such as infections and autoimmunity. However, the possible role of Fc glycans in tumor immunity is not yet fully understood. The aim of this study was to profile the Fc N-glycans of IgG samples from patients with gastric cancer (n = 80) and controls (n = 51) using LC-ESI-MS method to correlate the findings with stage of cancer and patients survival. Analysis of 32 different IgG N-glycans revealed significant increase of agalactosylated (GnGnF, GnGn(bi)F), and decrease of galactosylated (AGn(bi), AGn(bi)F, AA(bi), AAF) and monosialylated IgG glycoforms (NaAF, NaA(bi)) in cancer patients. A statistically significant increase of Fc fucosylation was observed in tumor stage II and III whereas reverse changes were found for the presence of bisecting GlcNAc. Higher level of fully sialylated glycans and elevated expression of glycans with bisecting GlcNAc were associated with better survival rate. Our findings provide the first evidence that the changes in Fc glycan profile may predict the survival of patients with gastric cancer. Cancer stage-dependent changes in Fc fucosylation and the bisecting N-acteylglucosamine expression as well as an association of several IgG glycoforms with the survival suggest that IgG glycosylation is related to pathogenesis of cancer and progression of the disease.

Specificity of serum anti-A(di) IgG antibodies from patients with gastrointestinal cancer.

Changes in the glycosylation in cancer may lead to an aberrant expression of A, B incompatible or xenogeneic blood group related antigens. To characterize the specificity of IgG antibodies to A, B, and related glycans in sera of gastrointestinal cancer patients, serum probes and affinity-isolated antibodies were analyzed in the indirect and competitive ELISA using a set of homogenous polyacrylamide (PAA) glycoconjugates. Monoreactive antibodies recognizing A(di) (I) and cross-reactive antibodies to A(di)/B(di)/B(tri) (II) or A(di)/A(tri)/Fs(di)/Core5 (III) were affinity-isolated on A(di)-PAA-Sepharose. The population I showed a higher affinity to A(di)-PAA than cross-reactive antibodies. The antibodies II were more specific to B(di) and may belong to the core alpha-Gal reactive antibodies but are also capable of recognizing A(di). The antibodies III were more specific to A(tri); they agglutinated A-erythrocytes and belong to anti-A isoantibodies reactive to xenogeneic oligosaccharides. The purified antibody samples were non- or faintly reactive to Tn. The IC(50) values of PAA glycoconjugates ranged from 6 × 10(-8) to 7 × 10(-6) M. No or weak binding of antibodies to the unrelated antigens used in the detection of polyreactivity (ferritin, casein, and DNA) was observed.

Postoperative change of anti-Thomsen-Friedenreich and Tn IgG level: the follow-up study of gastrointestinal cancer patients.

AIM: To study the influence of tumor removal on the serum level of IgG antibodies to tumor-associated Thomsen-Friedenreich (TF), Tn carbohydrate epitopes and xenogeneic alphaGal, and to elucidate on the change of the level during the follow-up as well as its association with the stage and morphology of the tumor and the values of blood parameters in gastrointestinal cancer. METHODS: Sixty patients with gastric cancer and 34 patients with colorectal cancer in stages I-IV without distant metastases were subjected to follow-up. The level of antibodies in serum was determined by the enzyme-linked immunosorbent assay (ELISA) using synthetic polyacrylamide (PAA) glycoconjugates. Biochemical and haematological analyses were performed using automated equipment. RESULTS: In gastrointestinal cancer, the TF antibody level was found to have elevated significantly after the removal of G3 tumors as compared with the preoperative level (u = 278.5, P < 0.05). After surgery, the TF and Tn antibody level was elevated in the majority of gastric cancer patients (sign test, 20 vs 8, P < 0.05, and 21 vs 8, P < 0.05, respectively). In gastrointestinal cancer, the elevated postoperative level of TF, Tn and alphaGal antibodies was noted in most patients with G3 tumors (sign test, 22 vs 5, P < 0.01; 19 vs 6, P < 0.05; 24 vs 8, P < 0.01, respectively), but the elevation was not significant in patients with G1 + G2 resected tumors. The postoperative follow-up showed that the percentage of patients with G3 resected tumors of the digestive tract, who had a mean level of anti-TF IgG above the cut-off value (1.53), was significantly higher than that of patients with G1 + G2 resected tumors (c2 = 3.89, all patients; c2 = 5.34, patients without regional lymph node metastases; P < 0.05). The percentage of patients with a tumor in stage I, whose mean anti-TF IgG level remained above the cut-off value (1.26), was significantly higher than that of patients with the cancer in stages III-IV (c2 = 4.71, gastric cancer; c2 = 4.11, gastrointestinal cancer; P < 0.05). The correlation was observed to exist between the level of anti-TF IgG and the count of lymphocytes (r = 0.517, P < 0.01), as well as between the level of anti-Tn IgG and that of serum CA 19-9 (r = 0.481, P < 0.05). No positive delayed-type hypersensitivity reaction in skin test challenges with TF-PAA in any of the fifteen patients, including those with a high level of anti-TF IgG, was observed. CONCLUSION: The surgical operation raises the level of anti-carbohydrate IgG in most patients, especially in those with the G3 tumor of the gastrointestinal tract. The follow-up demonstrates that after surgery the low preoperative level of TF antibodies may be considerably increased in patients with the carcinoma in its early stage but remains low in its terminal stages. The stage- and morphology-dependent immunosuppression affects the TF-antibody response and may be one of the reasons for unresponsiveness to the immunization with TF-antigens.

IgG Antibodies to GlcNAcß and Asialo-GM2 (GA2) Glycans as Potential Markers of Liver Damage in Chronic Hepatitis C and the Efficacy of Antiviral Treatment.

Total serum IgG level is a surrogate marker of hepatitis C (HC) severity. Antibodies (Abs) to microbial glycans could be markers of HC severity caused by the translocation of microbial products. The level of anti-glycan (AG) Abs was analysed in serum samples of patients (n = 128) with chronic HC in ELISA using fourteen synthetic glycans present in microbes and adhesins to evaluate the association of Abs with clinical parameters and the efficacy of antiviral treatment. The anti-GlcNAcß IgG level was significantly higher in patients with fibrosis (P = 0.021) and severe portal inflammation (P < 0.001) regardless of other clinical parameters. The ROC curve analysis showed sensitivity of 0.59, specificity of 0.84, and AUC of 0.71 in discriminating F0 from F1-4 (HCV genotype-1b-infected patients). The level of anti-GA2 Abs before Peg-IFN/RBV treatment was significantly higher in nonsustained viral response (non-SVR) to treatment than in SVR (P = 0.033). ROC analysis showed sensitivity of 0.62, specificity of 0.70, and AUC of 64. Correlations of AG Abs to clinical parameters were found. The quantification of anti-GlcNAcß Abs deserves attention in assessment of the hepatic damage while anti-GA2 Abs may be a sign of immune response related to the antiviral treatment.

Biomarkers of carcinogenic contaminants in Baltic flounder (Platichthys flesus): temporal changes in urban and non-urban sites in Tallinn bay.

In order to study effects of environmental contamination, a suite of biomarkers were measured over the period 1996 to 1999 in livers of flounder (Platichthys flesus) from two urban embayments and one non-urban reference site of the Gulf of Finland in the vicinity of Tallinn, Estonia. Total cytochrome P450 (CYP) level, aryl hydrocarbon hydroxylase (AHH), 5-aminolevulinic acid synthetase (ALA-S), and heme synthetase (HEM-S) activities were quantified by means of spectrophotometry. These data were compared to results obtained in 1994 for the same biomarkers at one of the urban embayments and the non-urban site, as measured by the same protocols. For the flounder collected from the non-urban site, changes occurred in AHH activity and the total CYP level, which were significantly lower in 1996 and 1999 compared with 1994 (p < 0.05). Activity of ALA-S decreased slightly over this same period. The activity of HEM-S increased between 1996 and 1999. In the urban site first investigated in 1994, the activities of AHH and ALA-S, as well as the total level of CYP in flounder liver were significantly higher compared with 1999 (p < 0.05). HEM-S activities did not show any significant changes over this time period. AHH activities of flounder collected in another urban site decreased slightly between 1996 and 1999, in contrast to data on the total CYP level which diminished drastically over these years (p < 0.05). Activities of HEM-S increased significantly (p < 0.05) during the period investigated, while activities of ALA-S remained unchanged. These findings suggest that contamination of the marine environments by PAHs has gone down everywhere in the Tallinn area during the last 3 to 5 years. However, the results indicate that the area is still contaminated, as indicated by elevated heme synthesis enzymes and the total CYP content, and that monitoring of contaminants and their effects should be continued in this region.

Increased sialylation of anti-Thomsen-Friedenreich antigen (CD176) antibodies in patients with gastric cancer: a diagnostic and prognostic potential.

AIM: To study whether alterations in the sialylation of antibodies (Ab) specific to the Thomsen-Friedenreich (TF) glycotope have a diagnostic and prognostic potential in gastric cancer. METHODS: Serum samples were taken from patients with gastric carcinoma (n = 142) and controls (n = 61). The level of TF-specific antibodies and their sialylation was detected using ELISA with synthetic TF-polyacrylamide conjugate as antigen and sialic acid-specific Sambucus nigra agglutinin (SNA). RESULTS: The level of TF-specific IgM was significantly decreased in cancer compared with controls (P ≤ 0.001). Cancer patients showed a higher level of SNA binding to anti-TF IgM and IgA (P ≤ 0.001) irrespective of disease stage, tumor morphology, and gender. Changes in the SNA/Ab index demonstrated moderate sensitivity (66-71%) and specificity (60-73%) for stomach cancer. The best diagnostic accuracy (100%) was achieved in 29% patients with high SNA binding and low anti-TF IgM level. This subset of patients demonstrated the poorest survival. CONCLUSION: Our findings are the first evidence that the increased sialylation of TF-specific Abs combined with a low level of anti-TF IgM is strongly linked to gastric cancer and patients survival, which can be used as a novel biomarker for cancer detection and prognosis.

Aberrant glycosylation of the anti-Thomsen-Friedenreich glycotope immunoglobulin G in gastric cancer patients.

AIM: To study whether alterations in the glycosylation of immunoglobulin G (IgG) specific to the Thomsen-Friedenreich glycotope (TF) have diagnostic and prognostic potential in gastric cancer. METHODS: Serum samples were obtained from patients with histologically verified gastric carcinoma (n = 89), healthy blood donors (n = 40), and patients with benign stomach diseases (n = 22). The lectin-enzyme-linked immunosorbent assay-based glycoprofiling of TF-specific IgG (anti-TF IgG) was performed using synthetic TF-polyacrylamide conjugate as antigen, total IgG purified by affinity chromatography on protein G sepharose, and lectins of various sugar specificities: mannose-specific concanavalin A (ConA), fucose-specific Aleuria aurantia lectin (AAL) and sialic acid-specific Sambucus nigra agglutinin (SNA). The sensitivity and specificity of the differences between cancer patients and controls were evaluated by receiver operator characteristic (ROC) curve analysis. Overall survival was analyzed by the Kaplan-Meier method. Time-dependent ROC curve statistics were applied to determine cut-off values for survival analysis. All calculations and comparisons were performed using the GraphPad Prism 5 and SPSS 15.0 software. RESULTS: The level of TF-specific IgG was significantly increased in cancer patients compared with non-cancer controls (P < 0.001). This increase was pronounced mostly in stage 1 of the disease. Cancer patients showed a higher level of ConA binding to anti-TF-IgG (P < 0.05) and a very low level of SNA lectin binding (P = 0.0001). No appreciable stage-dependency of the binding of any lectin to anti-TF IgG was found. A strong positive correlation between the binding of AAL and SNA was found in all groups studied (r = 0.71-0.72; P < 0.0001). The changes in ConA reactivity were not related to those of the fucose- or sialic acid-specific lectin. Changes in the SNA binding index and the ConA/SNA binding ratio demonstrated good sensitivity and specificity for stomach cancer: sensitivity 78.79% (95%CI: 61.09-91.02) and 72.73% (95%CI: 57.21-85.04); specificity 79.17 (95%CI: 65.01-89.53) and 88.64% (95%CI: 71.8-96.6), for the SNA binding index and the ConA/SNA binding ratio, respectively. The other combinations of lectins did not improve the accuracy of the assay. The low level of ConA-positive anti-TF IgG was associated with a survival benefit in cancer patients (HR = 1.56; 95%CI: 0.78-3.09; P = 0.19), especially in stages 3-4 of the disease (HR = 2.17; 95%CI: 0.98-4.79; P = 0.048). A significantly better survival rate was found in all cancer patients with a low reactivity of anti-TF IgG to the fucose-specific AAL lectin (HR = 2.39; 95%CI: 1.0-5.7; P = 0.038). CONCLUSION: The changes in the TF-specific IgG glycosylation pattern can be used as a biomarker for stomach cancer detection, and to predict patient survival.

Risks for HIV infection among gay, bisexual, and other men who have sex with men in Moscow and St. Petersburg, Russia.

The majority of early cases of HIV in Russia were among men who have sex with men (MSM). Despite this and the current resurgence of HIV among MSM globally, little systematic work has been done to assess current HIV risks. We conducted a rapid assessment of HIV and associated risk behaviors among MSM in Russia. An anonymous, cross-sectional study was performed among MSM in Moscow and St. Petersburg (January 2008). Participants were enrolled by local NGO partners via peer-recruitment, underwent a brief behavioral survey, and were offered rapid, oral HIV screening. Factors associated with HIV infection were assessed using logistic regression. A total of 401 participants were enrolled. HIV prevalence was comparable in the two cities (6.0% in Moscow, 5.5% in St. Petersburg). Approximately half (49.3%) were under age 25, 75.1% of all men reported unprotected anal intercourse (UAI), and 21.5% reported engaging in unprotected exchange sex in the prior 12 months. HIV infection was the highest (7.7%) among the youngest MSM, those aged 18-22 years. Never having tested for HIV (AOR=6.2; 95% CI: 1.8, 21.9) and ever injecting drugs (AOR=11.3; 95% CI: 2.6, 50.4) were independently associated with HIV infection. We found significant overall HIV prevalence among MSM in Moscow and St. Petersburg, particularly among the youngest men. The majority of men reported ongoing high-risk behaviors, indicating the potential for further spread. HIV prevention efforts need to specifically focus on urban MSM in Russia, encourage testing, and target injection risks to address this epidemic.

Better survival of Helicobacter pylori infected patients with early gastric cancer is related to a higher level of Thomsen-Friedenreich antigen-specific antibodies.

The survival of patients with histologically verified gastric carcinoma at stage I (n = 44) and stage II (n = 43) was analysed by the Kaplan-Meier method depending on H. pylori serological status and a level of IgG and IgM antibody to tumor-associated Thomson-Friedenreich antigen (T Ag). In cancer patients at stage I, significantly better survival for H. pylori seropositive patients was observed compared to H. pylori seronegative patients (median SE survival time: 60.0 +/- 3.8 mths and 37.0 +/- 7.8 mths, respectively; P < 0.0004, log-rank test). Patients with higher level of T Ag-specific IgG antibody (strong responders) showed significantly and dramatically better (P < 0.00001) survival rate than weak responders. However, an association of better survival with a higher level of anti-T antibody level was limited to the H. pylori seropositive patients exclusively (P < 0.00001) with no difference for H. pylori seronegative group of patients. The level of IgM anti-T Ag antibody was not significantly related to the survival of patients at both stages of the disease, though better survival was noted in H. pylori seropositive IgM strong responders at approximately 40-60 months of observation. Statistically insignificant associations between survival and H. pylori status or anti-T antibody levels were also observed in a group of gastric cancer patients at stage II. In summary, the survival of patients with early gastric cancer (stage I) is significantly better in H. pylori seropositive patients, and this phenomenon may be in part explained by up-regulation of T Ag-specific IgG immune response in H. pylori infected individuals.